Coronary heart disease (CHD) remains a leading cause of mortality. Over 50 million American adults have high serum cholesterol levels that place them at high risk for CHD. We propose to develop new efficacious and safe therapies biopolymer substrates as non-systemic hypercholesterolemic agent with significantly greater bile acid binding and therefore better cholesterol-lowering efficacy than cholestyramine. The objective of Phase I is to determine the feasibility of using biopolymers with inherent cholesterol-lowering properties and enhancing their efficacy by chemical modifications. The bile acid binding capacities of these materials will be evaluated by in vitro testing. The best candidates will be identified and selected for subsequent in vivo (animal) screening. The two most promising drug candidates for in vivo demonstration of their efficacy. This will include tests to determine: in vivo bile acid binding capacity. inhibition of plasma cholesterol elevation, fecal neutral sterol and bile acid excretion, and plasma cholesterol-lowering potential of the drug candidates. The identification of safe and potent non-systemic hypercholesterolemic agents is considered to provide a significant therapeutic benefit to a broad section of the population. PROPOSED COMMERCIAL APPLICATIONS: Half of the adult American population has elevated cholesterol levels that may increase their risk of developing coronary heart disease. The identification of a safe and potent non-systemic cholesterol-lowering drug could be of significant therapeutic benefit.